We propose to develop a novel, minimally invasive treatment for obstructive sleep apnea (OSA) that uses flavored substances as a chemo-attractant to engage the tongue, a process that may be described as chemoactivation. OSA is a disorder of symptomatic, repeated upper airway obstruction during sleep that is associated with substantial cardiovascular morbidity and mortality, endocrine disturbances, daytime somnolence, decreased quality of life, performance deficits, and motor vehicle crashes. 30-40% of OSA patients cannot tolerate first-line treatment (positive airway pressure) and may consider other options, including mandibular repositioning appliances and surgery. Oral appliances and surgery may offer substantial benefit for selected patients, but they carry many risks. The tongue has a pivotal role in OSA pathogenesis and treatment. The benefits of treatment with mandibular repositioning appliances and tongue- directed surgical procedures are based on repositioning and/or reduction in the size of the tongue. Novel tongue-directed therapies utilizing direct neuromuscular stimulation and oropharyngeal exercises have demonstrated encouraging initial results, but these too can be limited by cost, invasiveness, compliance, and/or limited effectiveness. Our strategy for meeting this challenge is an effective, safe, non-invasive device, for use by itself or during CPAP. The RestAssure? works by engaging the tongue during sleep by using flavored substances to promote tongue movement and swallowing. Using a prototype, first-in-man and pilot data are promising but require further evaluation. For Phase I of this SBIR proposal, we propose to optimize the efficacy of this approach in a study of 30 subjects with newly-diagnosed mild to moderate OSA (based on sleep study, or polysomnogram) and no previous treatment. In addition, we will begin miniaturization and optimization of the pump that will be used on the commercial device. Aim 1: Optimize efficacy and safety with respect to flavor compounds, infusion rates, and dosing intervals. All subjects will undergo overnight polysomnography with an intraoral mouthpiece designed to enable periodic infusion of flavored substances in the anterior oral cavity adjacent to the tongue tip. The primary outcome in assessing each parameter below will be the reduction in OSA severity (apnea-hypopnea index) from the sleep study (polysomnogram). Exploratory outcomes include usability, user acceptance, and changes in arousal index. Adverse events will be measured. 1a) Assess sweet (xylitol) versus salty (saline) versus control (water) flavors. 1b) Assess infusion rates. 1c) Assess duration and interval. Aim 2: Develop a prototype infusion device. The optimization in Aim 1 will utilize an existing portable benchtop infusion pump. For our commercial product, however, we will develop a body-worn infusion device, obviating the need for external tethers or equipment.